The skin, as an organ system, is extremely complex and mediates a diverse range of physiologic and immunologic functions that are essential for the maintenance of homeostasis. Besides providing an effective physical barrier, thermoregulatory capacity, the site for vitamin D production, and an effective means by which antigenic substances can be perceived immunologically (through Langerhans cell presentation), the skin also represents our largest sensory organ. Heat, cold, pain, and pressure represent one class of exogenous stimuli, which are perceived by the skin and converted into nerve impulses which are analyzed by the brain. Recent evidence now indicates that epidermal keratinocytes of the skin are capable of communicating external conditions to internal organ systems by the induced secretion of a multifunctional hormone. Originally named epidermal cell thymocyte activating factor (ETAF), this molecule is now known to be physiochemically and functionally identical to interleukin 1 (IL-1). Responsive targets for this molecule are quite diverse and include the liver, bone marrow, granulocytes, brain, muscle, fibroblasts, macrophages, pancreas, and lymphocytes, with the nature of any particular response being target-cell specific. We have found that ultraviolet light radiation (UVR) is capable of augmenting the production of ETAF/IL-1 in exposed animals, a condition which is paralleled by an enhanced liver synthesis of acute-phase reactants, neutrophila, and fever. Since our long-range goal on this project is to understand the immunoregulatory influences of UVR, knowledge concerning the impact of chronically enhanced production of ETAF/IL-1 following UVR-exposure is essential. By employing ideas, concepts, and technologies used to investigate the induction and regulation of other polypeptide hormones (insulin, EGF, etc.) we intend to: (1) establish whether ETAF/IL-1 is a stress hormone (production induced by cellular stress or insult); (2) determine the various means by which such a multifunctional molecule is regulated (production, target cell sensitivity, or buffering by specific carrier proteins); and (3) elucidate the mechanisms by which UVR-exposure of animals can alter host responsiveness to this hormone (specific desensitization to hormone-mediated effects). We hypothesize that a depression in responsiveness to ETAF/IL-1 would present an altered capacity to respond immunologically to minimal antigenic stimulation. (HF)